cDNA Cloning of the Rat IGF I Receptor: Structural Analysis of Rat and Human IGF I and Insulin Receptors Reveals Differences in Alternative Splicing and Receptor-Specific Domain Conservation

1994 ◽  
Vol 202 (2) ◽  
pp. 1038-1046 ◽  
Author(s):  
M.T. Pedrini ◽  
F. Giorgino ◽  
R.J. Smith
Keyword(s):  
Alternative Splicing ◽  
Structural Analysis ◽  
Cdna Cloning ◽  
Insulin Receptors ◽  
Specific Domain ◽  
Igf I ◽  
Domain Conservation

scholarly journals The human U1-70K snRNP protein: cDNA cloning, chromosomal localization, expression, alternative splicing and RNA-binding

1987 ◽  
Vol 15 (24) ◽  
pp. 10373-10391 ◽  
Author(s):  
Richard A. Spritz ◽  
Kathleen Strunk ◽  
Carol S. Surowy ◽  
Sallie O. Hoch ◽  
David E. Barton ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Cdna Cloning ◽  
Rna Binding ◽  
Chromosomal Localization ◽  
Snrnp Protein

cDNA cloning and structural analysis of the human limbic-system-associated membrane protein (LAMP)

Gene ◽  
1996 ◽  
Vol 170 (2) ◽  
pp. 189-195 ◽  
Author(s):  
Aurea F. Pimenta ◽  
Itzhak Fischer ◽  
Pat Levitt
Keyword(s):  
Structural Analysis ◽  
Membrane Protein ◽  
Cdna Cloning ◽  
Limbic System

scholarly journals Differential Activation of Insulin Receptor Substrates 1 and 2 by Insulin-Like Growth Factor-Activated Insulin Receptors

2007 ◽  
Vol 27 (10) ◽  
pp. 3569-3577 ◽  
Author(s):  
Adam Denley ◽  
Julie M. Carroll ◽  
Gemma V. Brierley ◽  
Leah Cosgrove ◽  
John Wallace ◽  
...  
Keyword(s):  
Growth Factor ◽  
Insulin Receptor ◽  
Splice Variants ◽  
Biological Effects ◽  
Insulin Receptors ◽  
Insulin Like Growth Factor ◽  
Extracellular Signal ◽  
Igf I ◽  
High Concentrations ◽  
Kinase Pathway

ABSTRACT The insulin-like growth factors (insulin-like growth factor I [IGF-I] and IGF-II) exert important effects on growth, development, and differentiation through the IGF-I receptor (IGF-IR) transmembrane tyrosine kinase. The insulin receptor (IR) is structurally related to the IGF-IR, and at high concentrations, the IGFs can also activate the IR, in spite of their generally low affinity for the latter. Two mechanisms that facilitate cross talk between the IGF ligands and the IR at physiological concentrations have been described. The first of these is the existence of an alternatively spliced IR variant that exhibits high affinity for IGF-II as well as for insulin. A second phenomenon is the ability of hybrid receptors comprised of IGF-IR and IR hemireceptors to bind IGFs, but not insulin. To date, however, direct activation of an IR holoreceptor by IGF-I at physiological levels has not been demonstrated. We have now found that IGF-I can function through both splice variants of the IR, in spite of low affinity, to specifically activate IRS-2 to levels similar to those seen with equivalent concentrations of insulin or IGF-II. The specific activation of IRS-2 by IGF-I through the IR does not result in activation of the extracellular signal-regulated kinase pathway but does induce delayed low-level activation of the phosphatidylinositol 3-kinase pathway and biological effects such as enhanced cell viability and protection from apoptosis. These findings suggest that IGF-I can function directly through the IR and that the observed effects of IGF-I on insulin sensitivity may be the result of direct facilitation of insulin action by IGF-I costimulation of the IR in insulin target tissues.

scholarly journals Purified hybrid insulin/insulin-like growth factor-I receptors bind insulin-like growth factor-I, but not insulin, with high affinity

1993 ◽  
Vol 290 (2) ◽  
pp. 419-426 ◽  
Author(s):  
M A Soos ◽  
C E Field ◽  
K Siddle
Keyword(s):  
Monoclonal Antibody ◽  
Growth Factor ◽  
Insulin Receptors ◽  
Beta Subunit ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf Receptors ◽  
Igf I ◽  
Growth Factor I

Hybrid insulin/insulin-like growth factor-I (IGF-I) receptors have previously been described in human placenta, but it has not been possible to study their properties in the presence of classical insulin receptors and type I IGF receptors. To facilitate the purification of hybrids, we produced an anti-peptide monoclonal antibody IGFR 1-2, directed against the C-terminal peptide of the type I IGF receptor beta-subunit. The antibody bound native human and rat type I IGF receptors, and reacted specifically with the beta-subunit on immunoblots. Solubilized placental microsomal membranes were depleted of classical type I IGF receptors by incubation with an immobilized monoclonal antibody IGFR 24-55, which reacts well with type I receptors but very poorly with hybrid receptors. Residual hybrid receptors were then isolated by incubation with immobilized antibody IGFR 1-2, and recovered by elution with excess of synthetic peptide antigen. Binding properties of hybrids were compared with those of immuno-affinity-purified insulin receptors and type I IGF receptors, by using the radioligands 125I-IGF-I and 125I-insulin. Hybrids bound approx. 20 times as much 125I-IGF-I as 125I-insulin at tracer concentrations (approx. 0.1 nM). The binding of 125I-insulin, but not 125I-IGF-I, to hybrids increased after treatment with dithiothreitol to reduce disulphide bonds between the alpha-subunits. Hybrids behaved very similarly to type I receptors with respect to the inhibition of 125I-IGF-I binding by unlabelled IGF-I and insulin. By contrast, the affinity of hybrids for insulin was approx. 10-fold lower than that of classical insulin receptors, as assessed by inhibition of 125I-insulin binding by unlabelled hormone. It is concluded that the properties of insulin receptors, but not IGF receptors, are markedly affected by assembly as hybrid compared with classical structures, and that hybrids are more likely to be responsive to IGF-I than insulin under physiological conditions.

scholarly journals Histone H4 stimulates glucose transport activity in rat skeletal muscle

1993 ◽  
Vol 295 (2) ◽  
pp. 549-553 ◽  
Author(s):  
L L Louters ◽  
E J Henriksen ◽  
C M Tipton
Keyword(s):  
Glucose Transport ◽  
Specific Binding ◽  
Insulin Receptors ◽  
Complex Signal ◽  
Scatchard Analysis ◽  
Maximal Effect ◽  
Histone H4 ◽  
Transport Activity ◽  
Igf I ◽  
Flexor Digitorum Brevis

We investigated the effects of purified histone H4 on glucose transport activity in rat soleus and flexor digitorum brevis muscles. Histone H4, at concentrations up to 11.8 microM, increased 2-deoxyglucose (2-DG) uptake in a dose-dependent fashion. However, at concentrations higher than 11.8 microM, H4 caused a decrease in 2-DG uptake from the maximum, suggesting a secondary inhibitory action of this compound. The maximal effect of H4 on 2-DG uptake was not additive to the maximal effect of insulin. Moreover, 2-DG uptake in the presence of both H4 and insulin was significantly lower than the 2-DG uptake in the presence of insulin alone. The maximal effect of H4 on stimulation of 2-DG uptake was neither additive nor inhibitory to the maximal effects of the intracellularly acting insulin mimetics sodium vanadate or H2O2. It was, on the other hand, additive to the maximal effects of muscle contractions. Also, in contrast with the effects of H4 on insulin-stimulated 2-DG uptake, H4 did not inhibit insulin-like growth factor-I (IGF-I)-stimulated 2-DG uptake, as the maximal effects of H4 and IGF-I were additive. Scatchard analysis of the binding of 125I-insulin in the absence or presence of histone H4 revealed that H4 increased the specific binding of insulin without affecting receptor affinity. These data suggest that H4 interacts with the insulin, rather than the hypoxia/contraction, pathway for activation of glucose transport in muscle tissue, and that H4 acts either directly or indirectly to increase the number of insulin receptors at the surface of the muscle cell. This interaction does not appear to occur with the similar, although distinct, IGF-I receptor. These studies may provide additional insight into the complex signal-transduction systems of insulin action.

Expression of insulin-like growth factor II (IGF-II) and IGF-II, IGF-I and insulin receptors mRNAs in isolated non-parenchymal rat liver cells

1992 ◽  
Vol 14 (1) ◽  
pp. 30-34 ◽  
Author(s):  
Frédérique Zindy ◽  
Eugenia Lamas ◽  
Sylvie Schmidt ◽  
André Kirn ◽  
Christian Brechot
Keyword(s):  
Growth Factor ◽  
Rat Liver ◽  
Insulin Receptors ◽  
Liver Cells ◽  
Insulin Like Growth Factor ◽  
Factor Ii ◽  
Igf I ◽  
Rat Liver Cells

scholarly journals Somatomedins/insulin-like growth factors, their receptors and binding proteins are present during mouse embryogenesis

Development ◽  
1987 ◽  
Vol 101 (1) ◽  
pp. 73-82
Author(s):  
E.P. Smith ◽  
T.W. Sadler ◽  
A.J. D'Ercole
Keyword(s):  
Growth Factors ◽  
Cell Line ◽  
Binding Proteins ◽  
Insulin Receptors ◽  
Embryonal Carcinoma Cell ◽  
Igf Binding Proteins ◽  
Embryonic Tissues ◽  
Embryonic Growth ◽  
Igf I ◽  
Insulin Like Growth Factors

Somatomedins/insulin-like growth factors (Sm/IGFs) are considered to have important roles in regulating fetal growth; however, because of limited quantities of tissue, few studies have been performed on their effects on embryonic growth. To assess a potential role for these factors, we evaluated mouse embryonic tissues for the presence of Sm/IGF and insulin receptors and Sm/IGF-binding proteins by chemical affinity labelling. In addition, we measured extractable Sm-C/IGF-I radioimmunoactivity in mouse embryonic tissues. Finally, we compared these data with those from the embryonal carcinoma cell line, PC13. All embryos from day 9 (3–4 somites) to day 12 (45 somites) possessed both Sm-C/IGF-I and IGF-II receptors in apparent greater abundance than insulin receptors. The visceral yolk sac appeared to have proportionally more insulin receptors than the corresponding embryonic tissue. Extracts from the embryos contained immunoreactive Sm-C/IGF-I and binding proteins of 30–45 X 10(3) Mr. PC13 cells possessed all three receptors and the apparent abundance of the insulin and IGF-II receptors was reduced after differentiation was induced with retinoic acid. PC13 cells released both immunoreactive Sm-C/IGF-I- and Sm-C/IGF-I-binding proteins into their medium. When differentiated, the binding proteins resembled the native ones extracted from the intact embryos. The presence of Sm/IGF activity, receptors and binding proteins in early embryogenesis suggests a role for these factors in embryonic growth. The PC13 cell line appears to only partially reflect normal development.

Analysis of the interaction of IGF I and structural mutants of IGF I with the IGF types 1 and 2 and insulin receptors

Peptides ◽  
1988 ◽  
pp. 570-571
Author(s):  
Margaret A. Cascieri ◽  
Gary G. Chicchi ◽  
Barbara G. Green ◽  
Joy Applebaum ◽  
Nancy S. Hayes ◽  
...  
Keyword(s):  
Insulin Receptors ◽  
Igf I
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